全文获取类型
收费全文 | 420篇 |
免费 | 52篇 |
出版年
2022年 | 3篇 |
2021年 | 4篇 |
2019年 | 6篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 15篇 |
2014年 | 20篇 |
2013年 | 16篇 |
2012年 | 31篇 |
2011年 | 22篇 |
2010年 | 19篇 |
2009年 | 11篇 |
2008年 | 23篇 |
2007年 | 22篇 |
2006年 | 21篇 |
2005年 | 11篇 |
2004年 | 34篇 |
2003年 | 20篇 |
2002年 | 7篇 |
2001年 | 19篇 |
2000年 | 14篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1992年 | 7篇 |
1991年 | 11篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 8篇 |
1981年 | 2篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1976年 | 2篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1967年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有472条查询结果,搜索用时 250 毫秒
41.
Shiran Shapira Oded Ben-Amotz Osnat Sher Dina Kazanov Jacob Mashiah Sarah Kraus Eyal Gur Nadir Arber 《PloS one》2015,10(10)
Background
Healthy individuals rarely have problems with wound healing. Most skin lesions heal rapidly and efficiently within one to two weeks. However, many medical and surgical complications can be attributed to deficiencies in wound repair. Open wounds have lost the barrier that protects tissues from bacterial invasion and allows the escape of vital fluids. Without expeditious healing, infections become more frequent. The CD24 gene encodes a heavily-glycosylated cell surface protein anchored to the membrane by phosphatidylinositol. CD24 plays an important role in the adaptive immune response and controls an important genetic checkpoint for homeostasis and autoimmune diseases in both mice and humans. We have previously shown that overexpression of CD24 results in increased proliferation and migration rates.Aim
To examine the role of CD24 in the wound healing process.Methods
An excisional model of wound healing was used and delayed wound healing was studied in genetically modified heat stable antigen (HSA/CD24)-deficient mice (HSA -/-) compared to wild-type (WT) mice.Results
Large full-thickness skin wounds, excised on the back of mice, exhibited a significant delay in the formation of granulation tissue, and in wound closure when compared to their WTHSA +/+ littermates. Wounds were histologically analyzed and scored, based on the degree of cellular invasion, granulation tissue formation, vascularity, and re-epithelialization. Additionally, in stitched wounds, the HSA -/- mice failed to maintain their stitches; they did not hold and fell already 24 hours, revealing erythematous wound fields. Re-expression of HSA, delivered by lentivirus, restored the normal healing phenotype, within 24 hours post-injury, and even improved the healing in WT, and in BalbC mice.Conclusions
Delayed wound-healing in the absence of HSA/CD24 suggests that CD24 plays an important role in this process. Increased expression of CD24, even in the normal state, may be used to enhance wound repair. 相似文献42.
Background and Aim
Proliferative vitreoretinopathy (PVR) is an active process that develops as a complication upon retinal detachment (RD), accompanied by formation of fibrotic tissue. The main cells involved in the development of fibrotic tissue during PVR are the retinal pigment epithelial (RPE) cells. The RPE cells undergo epithelial-mesenchymal transition (EMT) which leads to complex retinal detachment and loss of vision. Transforming growth factor-β1 (TGF-β1) is considered as the main player in the EMT of RPE cells, even though the mechanism is not fully understood. This study was performed to determine the possible involvement of transforming growth factor β activated kinase 1 (TAK1) in the EMT process of the RPE cells.Methodology
ARPE-19 Cells were treated with 5Z-7 oxozeaenol (TAK1 inhibitor) or SB431542 (TGF-β1 receptor kinase inhibitor) followed by TGF-β1 stimulation. Immunofluorescence, scratch assay Real time PCR and collagen contraction assay assessed the EMT features. The phosphorylation of Smad2/3 and p38 was examined using western blots analysis.Results
This study demonstrates that stimulation of RPE cells with TGF-β1 increases α-SMA expression, cell migration and cell contractility, all of which are EMT features. Remarkably, addition of TAK1 inhibitor abolishes all these processes. Furthermore, we show hereby that TAK1 regulates not only the activation of the non-canonical cascade of TGF-β1 (p38), but also the canonical cascade, the Smad2/3 activation. Thus, the outcome of the TGF-β response in RPE cells is TAK1 dependent.Conclusions/Significance
This work demonstrated TAK1, a component of the non-canonical pathway of TGF-β1, is a key player in the EMT process, thus provides deep insight into the pathogenesis of PVR. The ability to halt the process of EMT in RPE cells may reduce the severity of the fibrotic response that occurs upon PVR, leading to a better prognosis and increase the probability of success in RD treatment. 相似文献43.
Snir S Rao S 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2010,7(4):704-718
Accurate phylogenetic reconstruction methods are currently limited to a maximum of few dozens of taxa. Supertree methods construct a large tree over a large set of taxa, from a set of small trees over overlapping subsets of the complete taxa set. Hence, in order to construct the tree of life over a million and a half different species, the use of a supertree method over the product of accurate methods, is inevitable. Perhaps the simplest version of this task that is still widely applicable, yet quite challenging, is quartet-based reconstruction. This problem lies at the root of many tree reconstruction methods and theoretical as well as experimental results have been reported. Nevertheless, dealing with false, conflicting quartet trees remains problematic. In this paper, we describe an algorithm for constructing a tree from a set of input quartet trees even with a significant fraction of errors. We show empirically that conflicts in the inputs are handled satisfactorily and that it significantly outperforms and outraces the Matrix Representation with Parsimony (MRP) methods that have previously been most successful in dealing with supertrees. Our algorithm is based on a divide and conquer algorithm where our divide step uses a semidefinite programming (SDP) formulation of MaxCut. We remark that this builds on previous work of ours for piecing together trees from rooted triplet trees. The recursion for unrooted quartets, however, is more complicated in that even with completely consistent set of quartet trees the problem is NP-hard, as opposed to the problem for triples where there is a linear time algorithm. This complexity leads to several issues and some solutions of possible independent interest. 相似文献
44.
45.
Diverse subcellular locations of cryptogein-induced reactive oxygen species production in tobacco Bright Yellow-2 cells
下载免费PDF全文
![点击此处可从《Plant physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Reactive oxygen species (ROS) play a crucial role in many cellular responses and signaling pathways, including the oxidative burst defense response to pathogens. We have examined very early events in cryptogein-induced ROS production in tobacco (Nicotiana tabacum) Bright Yellow-2 suspension cells. Using Amplex Red and Amplex Ultra Red reagents, which report real-time H2O2 accumulation in cell populations, we show that the internal signal for H2O2 develops more rapidly than the external apoplastic signal. Subcellular accumulation of H2O2 was also followed in individual cells using the 2',7'-dichlorofluorescein diacetate fluorescent probe. Major accumulation was detected in endomembrane, cytoplasmic, and nuclear compartments. When cryptogein was added, the signal developed first in the nuclear region and, after a short delay, in the cell periphery. Interestingly, isolated nuclei were capable of producing H2O2 in a calcium-dependent manner, implying that nuclei can serve as a potential active source of ROS production. These results show complex spatial compartmentalization for ROS accumulation and an unexpected temporal sequence of events that occurs after cryptogein application, suggesting novel intricacy in ROS-signaling cascades. 相似文献
46.
47.
Eyngor M Chilmonczyk S Zlotkin A Manuali E Lahav D Ghittino C Shapira R Hurvitz A Eldar A 《FEMS microbiology letters》2007,277(2):238-248
By constructing a biological model based on in vitro culture of polarized rainbow trout primary skin epithelial cell monolayers, the series of early events that precede Streptococcus iniae infection, particularly colonization and translocation through external barriers, were analyzed. Streptococcus iniae promptly invades skin epithelial cells, but the rapid decline of viable intracellular bacteria points out the limited capability of intracellular survival for this bacterium. Translocation assays, supported by electron microscopy microphotographs, demonstrate that following successful in vitro invasion of skin epithelial cell, the bacterium exists free in the cytoplasm after release from the endosome, and translocates through the skin barrier. Bacterial invasion and transcytosis is not accompanied by apparent cell-line damages or disruption of host cells' tight junctions. It is hypothesized that the phenomenon of epithelial invasion coupled to the rapid translocation through the barrier plays a crucial role in Streptococcus iniae infection. 相似文献
48.
Sagi K Fujita K Sugiki M Takahashi M Takehana S Tashiro K Kayahara T Yamanashi M Fukuda Y Oono S Okajima A Iwata S Shoji M Sakurai K 《Bioorganic & medicinal chemistry》2005,13(5):1487-1496
An inhibitor of the complex of factor VIIa and tissue factor (fVIIa/TF), 2-substituted-4-amidinophenylpyruvic acid 1a, was structurally modified with the aim of increasing its potency and selectivity. The lead compound 1a was originally found in our factor Xa (fXa) inhibitor library on the basis of structural similarity of the primary binding sites of fVIIa and fXa. The design was based on computational docking studies using the extracted active site of fVIIa. Compound 1j was found to inhibit factor VIIa/TF at nanomolar concentration with improved selectivity versus fXa and thrombin and it preferentially prolonged the clotting time in the TF-dependent extrinsic pathway. 相似文献
49.
Ben-Abraham R Shapira I Szold A Weinbroum AA 《Canadian journal of physiology and pharmacology》2004,82(1):9-15
Remote ischemia-reperfusion detrimentally affects myocardial function by initially interfering with the rate of contraction. We investigated the usefulness of isoproterenol versus external electrical pacing in attenuating secondary functional damage of isolated Wistar rat atria. Atrial strips (n = 10/group) were bathed within oxygenated Krebs-Henseleit solution that exited from isolated livers that had been either perfused normally (controls) or underwent no flow (ischemia) for 2 h. In addition to one noninterventional ischemia-exposed strip group, a second group was externally paced at a fixed rate (55 pulses.min-1, 6 V) and a third "ischemia" group was treated with isoproterenol (0.1 mM), both interventions commencing upon the strips' exposure to the hepatic effluents. Control strips displayed unaltered contraction rate and systolic-generated tension during the 2-h exposure. Nontreated strips exposed to ischemic reperfusate experienced bradycardia compared with baseline values (7 +/- 2 vs. 50 +/- 12 beats.min-1, p < 0.05), followed <1-min later by a fall in the generated tension (11 +/- 4 vs. 20 +/- 6 mmHg, p < 0.05). The paced-ischemic strips displayed unaltered rate and force of contraction, whereas the addition of isoproterenol did not prevent deterioration in the rate and force of contraction (8 +/- 3 beats.min-1, 12 +/- 4 mmHg, respectively; p < 0.05 vs. baseline control ischemia-paced strips). Thus, external electrical pacing prevented liver ischemia-reperfusion-induced atrial strips' bradycardia and loss of contractility, while isoproterenol did not. 相似文献
50.